“DNA microarray” or “DNA chip” is a collective term that means slide glass or silicon base having DNA sequence fragments aligned in a high density thereon, which is an analytical tool used for gene expression analysis that have been recently developed. Transcription amount of each gene may be detected by using as an index intensity of hybridization of a prepared RNA or DNA sample (target). Such DNA microarray has now been used for the detection of single nucleotide polymorphism (SNP) as well.
The typical DNA chips that are known to be commercially available are an “Affimetrix-type” one sold by Affimetrix (USA) and a “Stanford-type” one developed by Stanford University (USA). The Affimetrix-type chip is made by synthesis of a DNA probe on silicon base in a high density so that it can fix from several thousands to several tens of thousands of kinds of probes on one chip. On the other hand, the Stanford-type chip is made by dropping DNA fragments that have been prepared in advance on slide glass. The detection with those chips is usually carried out by image analysis with the use of fluorescent pigments bound to the target.
Recently, a technique has been developed in which the results of hybridization between the probe and target are detected electrochemically in stead of fluorescent pigment (electrochemical Array: ECA chip) (Drummond, T. G.; Hill, M. G.; Barton, J. K. Natl. Biotechnol. 203, 21, 1192-1199). Such electrochemical detection is preformed with the use of an intercalating agent that is electroconductive and having a property of being intercalated between neighboring base pairs of a double-stranded DNA. There are already known electroconductive intercalating agents such as anthraquinone, naphthquinone, polyphyne and ferrocene. An example of the detection of a gene using ferrocene derivatives was reported (Fan, C.; Plaxco, K. W.; Heeger, A. J. Proc. Natl. Acad. Sci. USA, 2003, 100, 9134-9137). Furthermore, a DNA chip with the use of ferrocenyl naphthalene diimide derivatives as the intercalating agent and various methods using said chip have been proposed (Japanese Patent Application Publications No. 2003-300 and No. 2003-83968).
On the other hand, hairpin-type pyrrole-imidazole-polyamide (PIPA) usually forming 6-mer or 8-mer is known as a prototype of synthetic organic molecules that can site-specifically recognize a DNA sequence, and its potentiality for gene regulation has been therefore proposed (Mrksich, M.; Parks, M. E.; Derevan, P. B. J. Am. Chem. Soc. 1994, 116, 7983-7988). Furthermore, many attempts have been reported in which the structure of PIPA was modified in order to alter their functions and properties. For example, some research groups have proposed modification of PIPA with a fluorescent pigment (Rucker, V. C.; Foister, S.; Melander, C.; Dervan, P. B. J. Am. Chem. Soc. 2003, 125, 1195-1202), oranalkylating agent (Wang, Y-D.; Dziegielewski, J.; Wurtz, N. R.; Dzielewska, B.; Dervan, P. B.; Beerman, T. A. Nucleic Acids Res. 2003, 31, 1208-1215, et al.), in order to use it as a tool for the detection of a gene and a potential anti-cancer agent.
In addition to the above functional modification, some other research groups tried the modification of the structure of PIPA into other heterocyclic compounds for the purpose of improvement of affinity and sequence-specificity of pyrrole and imidazole for the double-stranded DNA, and some of them reported success of the improvement of sequence-specificity (Foister, S.; Marques, M. A.; Doss, R. M.; Dervan, P. B. Bioorganic Med. Chem. Lett. 2003, 11, 4333-4340, et al.)                [Patent Document 1] Japanese Patent Application Publications No. 2003-300        [Patent Document 2] Japanese Patent Application Publications No. 2003-83968        [Non-Patent Document 1] Fan, C.; Plaxco, K. W.; Heeger, A. J. Proc. Natl. Acad. Sci. USA, 2003, 100, 9134-9137        [Non-Patent Document 2] Mrksich, M.; Parks, M. E.; Derevan, P. B. J. Am. Chem. Soc. 1994, 116, 7983-7988        [Non-Patent Document 3] Rucker, V. C.; Foister, S.; Melander, C.; Dervan, P. B. J. Am. Chem. Soc. 2003, 125, 1195-1202        [Non-Patent Document 4] Wang, Y-D.; Dziegielewski, J.; Wurtz, N. R.; Dzielewska, B.; Dervan, P. B.; Beerman, T. A. Nucleic Acids Res. 2003, 31, 1208-1215        [Non-Patent Document] Foister, S.; Marques, M. A.; Doss, R. M.; Dervan, P. B. Bioorganic Med. Chem. Lett. 2003, 11, 4333-4340        